title: A systematic multitechnique approach for detection and characterization of reversible self-association during formulation development of therapeutic antibodies.
abstract: In addition to controlling typical instabilities such as physical and chemical degradations, understanding monoclonal antibodies' (mAbs) solution behavior is a key step in designing and developing process and formulation controls during their development. Reversible self-association (RSA), a unique solution property in which native, reversible oligomeric species are formed as a result of the noncovalent intermolecular interactions has been recognized as a developability risk with the potential to negatively impact manufacturing, storage stability, and delivery of mAbs. Therefore, its identification, characterization, and mitigation are key requirements during formulation development. Considering the large number of available analytical methods, choice of the employed technique is an important contributing factor for successful investigation of RSA. Herein, a multitechnique (dynamic light scattering, multiangle static light scattering, and analytical ultracentrifugation) approach is employed to comprehensively characterize the self-association of a model immunoglobulin G1 molecule. Studies herein discuss an effective approach for detection and characterization of RSA during biopharmaceutical development based on the capabilities of each technique, their complementarity, and more importantly their suitability for the stage of development in which RSA is investigated.
authors.affiliation: Department of Formulation Sciences, MedImmune, Gaithersburg, Maryland 20878, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Esfandiary
authors.forename: David B
authors.initials: DB
authors.lastname: Hayes
authors.forename: Arun
authors.initials: A
authors.lastname: Parupudi
authors.forename: Jose
authors.initials: J
authors.lastname: Casas-Finet
authors.forename: Shufeng
authors.initials: S
authors.lastname: Bai
authors.forename: Hardeep S
authors.initials: HS
authors.lastname: Samra
authors.forename: Ambarish U
authors.initials: AU
authors.lastname: Shah
authors.forename: Hasige A
authors.initials: HA
authors.lastname: Sathish
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008027:Light; D012542:Scattering, Radiation; D012996:Solutions; D014461:Ultracentrifugation / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D012996:Solutions
keywords: analytical ultracentrifugation; biotechnology; formulation; high-throughput technologies; intermolecular interaction; light scattering (dynamic); light scattering (static); monoclonal antibody; reversible self-association; screening